Pembrolizumab Post-IMRT for Thyroid Cancer

Overseen By Gina Tamsen

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: M.D. Anderson Cancer Center

Must not be taking: Immunosuppressants, Steroids

Disqualifiers: Autoimmune disease, Pneumonitis, HIV, others

Stay on Your Current Meds You can continue your current medications while participating

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 6 months

35 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial tests if pembrolizumab, given after radiation therapy, can help patients with advanced anaplastic thyroid cancer in the neck live longer without their disease getting worse. Pembrolizumab works by boosting the immune system to attack cancer cells and is used to treat various cancers.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, if you are on chronic systemic steroid therapy or immunosuppressive therapy, you may need to stop or adjust these, as they are part of the exclusion criteria.

What data supports the effectiveness of the drug pembrolizumab for thyroid cancer?

Research shows that pembrolizumab has been effective in treating other cancers, like melanoma and non-small cell lung cancer, by shrinking tumors and improving survival rates. Additionally, studies have evaluated its safety and effectiveness in patients with advanced thyroid cancer, suggesting it may be a promising option for those who have not responded to standard treatments. ^{1 2 3 4 5}

Is pembrolizumab generally safe for humans?

Pembrolizumab, also known as Keytruda, has been used in cancer treatment and is generally considered safe, but it can cause side effects. Common side effects include fatigue, cough, nausea, and skin rash. It can also cause immune-related issues like thyroid problems and, rarely, type 1 diabetes. ^{1 5 6 7 8}

How does the drug pembrolizumab differ from other treatments for thyroid cancer?

Pembrolizumab is unique because it is an immunotherapy drug that works by blocking the PD-1 receptor, helping the immune system attack cancer cells. This approach is different from traditional treatments like surgery or radioactive iodine, as it uses the body's own immune system to target the cancer. ^{1 2 3 5 6}

Research Team

Maria Cabanillas, MD

Principal Investigator

M.D. Anderson Cancer Center

Eligibility Criteria

This trial is for adults with stage IVB anaplastic thyroid cancer (ATC) who have completed radiation therapy, possibly with chemotherapy. They must be in good health overall, not pregnant or breastfeeding, and willing to use contraception. Those with certain prior treatments or immunodeficiencies, recent vaccinations, or specific genetic mutations are excluded.

Inclusion Criteria

Written informed consent for the trial

My cancer is advanced but hasn’t spread to my neck.

I am 18 or older with a diagnosis of anaplastic thyroid cancer.

Exclusion Criteria

I have not received a live vaccine in the last 30 days.

I have an immune system disorder or have been on steroids or other immune-weakening drugs in the last week.

I have had previous treatments targeting my immune system.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Radiation

Participants receive external beam radiation to the primary tumor, with or without concomitant chemotherapy

6-8 weeks

Treatment

Participants receive adjuvant pembrolizumab infusions every 6 weeks

6 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

6 months

Treatment Details

Interventions

• Pembrolizumab

Trial Overview The trial tests pembrolizumab as an additional treatment after radiation for ATC. It aims to see how long patients can live without their cancer getting worse after this combination of therapies. Participants will receive pembrolizumab following either high-dose (>51 Gy) or lower-dose (<50 Gy) radiation.

Participant Groups

Group I: Pembrolizumab Experimental Treatment 1 Intervention

The infusions are given every 6 weeks

Who Is Running the Clinical Trial?

M.D. Anderson Cancer Center

Lead Sponsor

Trials

3,107

Recruited

1,813,000+

Findings from Research

Pembrolizumab (KEYTRUDA) was approved by the FDA for treating advanced melanoma, showing an overall response rate of 24% in a trial of 89 patients, with 86% of responses lasting at least 6 months.

While there are potential immune-mediated side effects, the benefits of prolonged tumor response durations were deemed to outweigh these risks, marking an improvement over existing treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Accelerated Approval of Pembrolizumab for Second-Line Treatment of Metastatic Melanoma. Chuk, MK., Chang, JT., Theoret, MR., et al.[2021]

In a study of 103 patients with advanced thyroid cancer, pembrolizumab showed a modest objective response rate of 6.8%, with a median duration of response lasting 18.4 months, indicating some effectiveness in this challenging cancer type.

The treatment was associated with manageable toxicity, as 69.9% of patients experienced treatment-related adverse events, but only 14.6% had severe (grade 3-5) reactions, suggesting that pembrolizumab can be safely administered to this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of pembrolizumab monotherapy in patients with advanced thyroid cancer in the phase 2 KEYNOTE-158 study. Oh, DY., Algazi, A., Capdevila, J., et al.[2023]

Pembrolizumab, an immune checkpoint inhibitor, has demonstrated significant efficacy in reducing tumor size and improving survival rates in patients with non-small cell lung carcinoma (NSCLC).

However, the treatment is associated with an increased risk of immune-related adverse effects, including cases of type 1 diabetes mellitus and autoimmune thyroiditis, highlighting the need for careful monitoring during therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab: An Immunotherapeutic Agent Causing Endocrinopathies. Chaudry, A., Chaudry, M., Aslam, J.[2020]

In a phase Ib trial involving 22 patients with advanced differentiated thyroid cancer, pembrolizumab showed a manageable safety profile, with 82% experiencing treatment-related adverse events, primarily diarrhea and fatigue, but no treatment-related deaths.

The treatment demonstrated limited efficacy, with an objective response rate of 9% and a median progression-free survival of 7 months, indicating that while some patients may benefit, further research is needed to confirm these results.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and antitumor activity of the anti-PD-1 antibody pembrolizumab in patients with advanced, PD-L1-positive papillary or follicular thyroid cancer. Mehnert, JM., Varga, A., Brose, MS., et al.[2020]

Pembrolizumab (KEYTRUDA) was approved by the FDA for treating unresectable or metastatic melanoma based on two clinical trials involving 1,374 patients, showing significant improvements in overall survival compared to ipilimumab, with hazard ratios indicating a reduced risk of death.

Patients receiving pembrolizumab also experienced significant improvements in progression-free survival, although some immune-mediated adverse reactions like hypothyroidism and pneumonitis were noted, highlighting the importance of monitoring for side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Pembrolizumab for the Treatment of Patients with Unresectable or Metastatic Melanoma. Barone, A., Hazarika, M., Theoret, MR., et al.[2022]

Pembrolizumab, a PD-1 inhibitor used in cancer treatment, can lead to rare but serious immune-related adverse events, including type 1 diabetes mellitus, occurring in about 0.2% of cases.

A review of 42 cases revealed that patients may develop diabetic ketoacidosis during treatment, highlighting the need for blood glucose monitoring and awareness of this potential side effect among clinicians.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Programmed Cell Death-1 Inhibitor-Induced Type 1 Diabetes Mellitus. Clotman, K., Janssens, K., Specenier, P., et al.[2022]

Immune checkpoint inhibitors like pembrolizumab can lead to various immune-related adverse events, with thyroid dysfunction being a common issue.

This report highlights a rare case of Graves' disease causing thyrotoxicosis in a 50-year-old patient undergoing pembrolizumab therapy, emphasizing the need for awareness of this potential side effect.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Rare Case of Pembrolizumab-Associated Graves' Disease. Alqaisi, S., Rahman, A.[2023]

References

1. United States pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Accelerated Approval of Pembrolizumab for Second-Line Treatment of Metastatic Melanoma. [2021]

2. United States pubmed.ncbi.nlm.nih.gov

Efficacy and safety of pembrolizumab monotherapy in patients with advanced thyroid cancer in the phase 2 KEYNOTE-158 study. [2023]

3. United States pubmed.ncbi.nlm.nih.gov

Pembrolizumab: An Immunotherapeutic Agent Causing Endocrinopathies. [2020]

4. England pubmed.ncbi.nlm.nih.gov

Safety and antitumor activity of the anti-PD-1 antibody pembrolizumab in patients with advanced, PD-L1-positive papillary or follicular thyroid cancer. [2020]

5. United States pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Pembrolizumab for the Treatment of Patients with Unresectable or Metastatic Melanoma. [2022]

6. United States pubmed.ncbi.nlm.nih.gov

Programmed Cell Death-1 Inhibitor-Induced Type 1 Diabetes Mellitus. [2022]

7. United States pubmed.ncbi.nlm.nih.gov

A Rare Case of Pembrolizumab-Associated Graves' Disease. [2023]

8. United States pubmed.ncbi.nlm.nih.gov

Incidence of Thyroid-Related Adverse Events in Melanoma Patients Treated With Pembrolizumab. [2022]